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Adverse drug events (ADEs) in outpatient settings can cause significant morbidity and mortality. Updating a prior study, this surveillance study identified more than 40,000 ADEs among 58 emergency departments in the United States. Investigators estimated that 4 emergency department visits for ADEs occurred per 1000 patients annually during the study period, with more than one-quarter of these visits resulting in hospitalization. Antibiotic reactions were the most common ADE for children. Among patients age 65 or older, anticoagulants, diabetes medications, and opioids were most commonly implicated in ADEs, as seen in a previous study. Medications considered inappropriate for older adults according to Beers criteria were involved in less than 2% of ADEs. The authors conclude that preventing ADEs requires attention to older adults and to antibiotic, anticoagulant, diabetes, and opioid medications, consistent with recommendations from the 2014 National Action Plan for Adverse Drug Event Prevention.